scholarly journals NTRK3-rearranged thyroid carcinoma, clinical and pathologic features

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S50-S50
Author(s):  
C Skibiel ◽  
S Ren ◽  
L Reid

Abstract Introduction/Objective NTRK3 gene encodes a transmembrane protein receptor of the tropomyosin receptor kinase (Trk) family. Gene fusions involving NTRK3 result in a constitutive activation or overexpression of Trk receptor, potentially leading to oncogenesis. NTRK targeted therapies show a promising activity in varied cancer types with NTRK fusions. The aim of this case review is to describe the clinical and pathologic findings of thyroid neoplasm with NTRK3 gene fusions. Methods/Case Report The cytology fine needle aspiration (FNA), molecular testing results and pathology of surgical resections are reviewed in 220 cases of total and hemithyroidectomy from January 2018 to May 2021. Results (if a Case Study enter NA) Three cases with NTRK3 gene fusions are identified by Thyroseq or Afirma GSC from FNA of thyroid nodules with later surgical intervention. No other mutations or gene fusions were identified. Each case had total thyroidectomy. Case 1 is a 41-year-old female with FNA diagnosis of suspicious for papillary thyroid carcinoma (PTC) and ETV6/NTRK3 fusion found by Afirma GSC. Pathology diagnosis is PTC classic type, two tumor nodules 1.1cm and 1.0cm, lymphovascular invasion not identified, three lymph nodes not involved by tumor and pathologic stage pT1b(m) pN0. Case 2 is a 49-year-old female with FNA diagnosis of atypia of undetermined significance and ETV6/NTRK3 fusion detected by Thyroseq. Pathology diagnosis is infiltrative PTC follicular variant, 2.0cm, angioinvasion present, no lymph nodes submitted and pathologic stage pT1b(m) pNX. Case 3 is a 28-year-old female with FNA diagnosis of suspicious for follicular derived neoplasm and NTRK3/RBPMS fusion is detected by Afirma GSC. Pathology diagnosis is infiltrative PTC follicular variant, 1.5cm, 9 of 11 lymph nodes positive for metastatic carcinoma and pathologic stage pT1b pN1b. Conclusion Thyroid neoplasm with NTRK3-rearrangement is rare. Cases 1 and 2 with common ETV6-NTRK3 fusion show PTC classic type and infiltrative PTC follicular variant with angioinvasion. Case 3 with less common NTRK3/RBPMS fusion shows infiltrative PTC follicular variant and significant lymph node involvement. Our limited cases of NTRK3-rearranged thyroid carcinoma demonstrate infiltrative growth, diverse phenotypes, one case with angioinvasion and no lymph nodes submitted and one case with multiple lymph node metastasis. This suggests aggressive behavior of thyroid cancer with NTRK3 gene fusion and patients may benefit from targeted NTRK therapy.

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S53-S54
Author(s):  
C Skibiel ◽  
S Ren ◽  
L Reid

Abstract Introduction/Objective Thyroid adenoma-associated (THADA)-IGF2BP3 fusions is related to strong overexpression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) mRNA and protein, increased IGF2 translation and IGF1 receptor signaling via PI3K and MAPK pathways. THADA-IGF2BP3 have been identified as an oncogenic event in thyroid neoplasms, but the clinicopathologic features have not been greatly evaluated. The purpose of this cases review is to describe the clinical and pathologic findings of thyroid nodules with THADA-IGF2BP3 fusion on molecular testing. Methods/Case Report Surgical Pathology 220 cases of total and hemithyroidectomy from January 2018 to December 2019 were reviewed for cytology fine needle aspiration (FNA), molecular testing results and surgical resection pathology. Results (if a Case Study enter NA) Three cases of THADA-IGF2BP3 fusion identified by Thyroseq testing from FNA of thyroid nodules with all diagnosed as atypia of undetermined significance, Bethesda category 3. No other mutations or gene fusions are identified. Successive surgical interventions are performed. Case 1 is a 49-year-old female right hemithyroidectomy with pathologic diagnosis of papillary thyroid carcinoma (PTC) follicular variant with tumor capsular invasion and no lymphvascular invasion. The tumor is 2cm, two lymph nodes evaluated are not involved by tumor and pathological stage is pT1b pN0. Case 2 is a 71-year-old female total thyroidectomy and the pathologic diagnosis is PTC follicular variant with tumor capsular invasion and no lymphvascular invasion. The tumor is 2cm, one lymph node evaluated is not involved by tumor and pathologic stage is pT1b pN0. Case 3 is a 76-year-old male left hemithyroidectomy and pathologic diagnosis is PTC follicular variant with tumor capsular invasion and no lymphvascular invasion. The tumor is 2cm, two lymph nodes evaluated are not involved by tumor and pathologic stage is pT1b pN0. Conclusion THADA-GF2BP3 fusion is uncommon in thyroid neoplasms and only three cases are detected in 220 cases evaluated. The three cases of thyroid nodules are all diagnosed as AUS by FNA, and all are diagnosed as PTC follicular variant with capsular invasion upon resection without lymphvascular invasion or lymph node involvement. THADA-F2BP3 fusion is associated with thyroid carcinoma, with low-risk non-aggressive behavior, conservative surgery appears necessary and lobectomy is likely adequate.


2016 ◽  
Vol 23 (3) ◽  
pp. 31-37
Author(s):  
Fatimah A. Alturkistani ◽  
Murad A. Alturkustani

Pathological diagnosis of follicular variant of papillary thyroid carcinoma has high inter and intra-observer variability among expert pathologists, aff ecting prognosis and management of the disease. A recent study applying strict diagnostic criteria and long-term follow up confi rmed the indolent behavior of a subtype of these tumors. They recommended a nomenclature change to noninvasive follicular thyroid neoplasm with papillary-like nuclear features, refl ecting the low risk of adverse outcomes. We searched the pathology archives of King Abdulaziz University Hospital from 2002-2016 for all cases diagnosed with “follicular variant of papillary thyroid carcinoma”. Clinical data, and imaging fi ndings were retrospectively reviewed. Available pathologyslides were reviewed using the proposed inclusion and exclusion diagnostic criteria. We confi rmed the diagnostic reproducibility of the suggested criteria. Ten out of 37 cases met the diagnostic criteria. Eightadditional patients could have had their diagnosis modifi ed if sufficient tissue samples were available. Follow up data confi rmed the indolent behavior in these cases with no recurrence or adverse outcome. We concluded that application of the new diagnostic criteria for this subtype is reasonable and has major ramifi cations for the diagnosis and management as this will spare unnecessary thyroidectomies, radioactive iodine therapy, and their complications.


2020 ◽  
Vol 48 (11) ◽  
pp. 030006052096649
Author(s):  
Fuxin Li ◽  
Wei Li ◽  
Katherine D. Gray ◽  
Rasa Zarnegar ◽  
Dan Wang ◽  
...  

Objectives Follicular variant papillary thyroid carcinoma (FVPTC) is treated similarly to classical variant papillary thyroid carcinoma (cPTC). However, FVPTC has unique tumour features and behaviours. We investigated whether a low dose of radioiodine was as effective as a high dose for remnant ablation in patients with FVPTC and evaluated the recurrence of low-intermediate risk FVPTC. Methods Data from cPTC and FVPTC patients treated with I-131 from 2004 to 2014 were reviewed. Demographics, tumour behaviour, lymph node metastasis, and local recurrence data were compared between FVPTC and cPTC patients. Then, low-intermediate risk FVPTC patients were divided into low, intermediate, and high I-131 dose groups, and postoperative I-131 activities were analysed to evaluate the effectiveness of I-131 therapy for thyroid remnant ablation. Results In total, 799 cases of FVPTC (n = 168) and cPTC (n = 631) treated with I-131 were identified. Patients with FVPTC had a larger primary nodule size than cPTC, but lymph node metastases and local recurrence were more prevalent in cPTC than in FVPTC. For the low-, intermediate-, and high-dose groups, success rates of ablation did not differ (82.0%, 80%, and 81.3%, respectively). Conclusion FVPTC differs from cPTC in behaviour. Low-dose ablation may be sufficient in FVPTC patients with low-intermediate disease risk.


2020 ◽  
Author(s):  
Wei Liu ◽  
Zhenglin Wang ◽  
Cong Wang ◽  
Zhilong Ai

Abstract Background: Some studies have reported that Delphian lymph node (DLN) metastasis is associated with a poor prognosis of papillary thyroid carcinoma (PTC), but the number of the available studies is limited and the results are inconsistent. The aim of this investigation was to study the incidence and clinical significance of DLN metastasis in patients with unilateral PTC.Methods: This was a cross-sectional study from January 2016 to December 2019. The data were obtained from the department of general surgery in Shanghai Zhongshan Hospital affiliated to Fudan University. This study included 522 patients with unilateral PTC and had DLN harvested. The associations between DLN metastasis and the clinical characteristics of the patients, i.e. age, sex, tumor size, multifocality, capsular invasion, extrathyroidal extension, central lymph nodes (CLN) metastasis (excluding DLN), and lateral lymph nodes (LLN) metastasis was analyzed.Results: Among all the 522 patients, 133 (25.5%) patients had metastasized DLN lymph nodes. DLN metastasis was significantly associated with age (p = 0.047), male (p < 0.001), larger tumor size (p < 0.001), capsular invasion (p < 0.001), extrathyroidal extension (p = 0.004), tumor location in upper third (p = 0.003), other CLN metastasis (p < 0.001), number of positive CLN (excluding DLN) (p < 0.001), LLN metastasis (p = 0.036), number of positive LLN (p = 0.004) and number of DLN removed (p = 0.043). No association was found between DLN metastasis and multifocality, number of CLN removed and number of LLN removed.Conclusions: DLN metastasis is associated with some adverse prognostic markers of PTC. If the DLN is positive on intraoperative frozen section, careful dissection of CLN and careful evaluation of LLN are essential, and intensive follow-up should be warranted.


2020 ◽  
Author(s):  
Ling Zhan ◽  
Hong-fang Feng ◽  
Xi-zi Yu ◽  
Ling-rui Li ◽  
Jun-long Song ◽  
...  

Abstract Objective: It has been reported that papillary thyroid carcinoma (PTC) patients with lymph node metastasis (LNM) are more associated with adverse outcomes. This study aimed to assess the correlation between the lymph node (LN) status and clinical prognosis in PTC patients. Methods: We retrospectively reviewed the medical records of PTC patients who underwent initial thyroid cancer surgery in Renmin Hospital of Wuhan University between 2017 and 2019. 1021 PTC patients with total checked number of lymph nodes ≥5 were involved in this study. The clinicopathological characteristics of patients were compared according to the LN status and the number of metastatic lymph nodes (NMLNs). Results: The LNM and NMLNs>5 were seen in 694 (68.0%) and 222 (21.7%) cases, respectively. Young patients, patients with larger tumor diameter, bilaterality, multifocality and gross extrathyroidal extension (ETE) were more inclined to LNM and NMLNs >5 (P<0.001). The patients with LNM (pN1) were mainly among males and were exhibited multifocality and advanced tumor stage (P<0.001), while pN1 patients with NMLNs >5 were negatively associated with advanced tumour stage (P<0.05). Recurrence-free survival among pN1 patients was significantly different between 2 groups (NMLNs ≤5: 0/472, 100.0%; NMLNs >5: 5/222, 97.7%; P=0.002). In multivariate logistic regression analysis, the male (OR=2.580, P<0.001), 10-mm tumor size (OR=1.770, P<0.001), tumor gross ETE (OR=2.004, P<0.001) were independent predictors for the high prevalence of LNM. Similarly, 10-mm tumor size (OR=1.399, P<0.05), bilaterality (OR=2.350, P<0.001) and tumor gross ETE (OR=2.660, P<0.05) were also independent predictors for the high prevalence of NMLNs >5; 10-year age was an independent predictor for the low prevalence of the LNM (OR=0.658, P<0.001) and NMLNs >5 (OR=0.678, P<0.001). Conclusions: The status of the cervical LNs and the NMLNs should be correctly evaluated to guide reasonable treatment and careful follow-up.


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